The overall objectives of this investigation are (a) to develop a molecular description and the mechanisms of control for inhibition of mitosis in the differentiated cell, for the biogenesis of the tonofilaments in the basal and lower spinous cells, for the formation of keratohyalin in the granular cells and for the loss of the nucleus and keratohyalin as the granular cell enters the stratum corneum, and (b) to define the molecular lesions responsible for the pathology in psoriasis, squamous cell and basal cell carcinomas and possibly other diseases of aberrant differentiation by developing and applying technology suitable for investigating abnormalities in the parameters elucidated in (a) to biopsy specimens of the pathological lesions. Methods to be applied include the biochemical isolation of the G1 inhibitor from differentiated cells and an evaluation of its status in hyperproliferative diseases, the use of antibodies to a tonofilament-protein to evaluate the protein's status in pathologies involving aberrant tonofilaments, an identification of changes in the carbohydrate of cell membranes during the differentiation of the keratinocyte and an elucidation of the role of histidine-rich protein in keratohyalin formation and the nature of the aberration responsible for absence of keratohyalin in parakeratotic conditions.